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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 8  |  Issue : 2  |  Page : 74-79

Clinical profile of prosthetic heart valve thrombosis and outcome analysis of fibrinolytic therapy versus surgical management: A single-center experience


1 Department of Cardiology, U. N. Mehta Institute of Cardiology and Research Centre, B. J. Medical College, Ahmedabad, Gujarat, India
2 Department of Research, U. N. Mehta Institute of Cardiology and Research Centre, B. J. Medical College, Ahmedabad, Gujarat, India

Date of Submission03-Feb-2020
Date of Decision28-Apr-2020
Date of Acceptance08-May-2020
Date of Web Publication4-Aug-2020

Correspondence Address:
Vishal Sharma
Department of Cardiology, U. N. Mehta Institute of Cardiology and Research Centre, Civil Hospital Campus, Asarwa, Ahmedabad - 380 016, Gujarat
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/heartindia.heartindia_5_20

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  Abstract 


Context: The main aim of the study is to find out efficacy, outcomes, and complications of thrombolytic therapy and surgery for obstructive prosthetic heart valve thrombosis (PHVT).
Materials and Methods: This was a prospective, observational study done on 130 patients with PHVT, from January 2016 to December 2017. Baseline details, clinical investigations, echocardiography, and fluoroscopy were done. In fibrinolytic therapy, group agents used were streptokinase and urokinase. Out of 130, 115 patients were followed for up to 6 months after the discharge.
Results: Majority of the patients were females (66.9%). Sixty-five (50%) patients were in the New York Heart Association Class III, whereas 55 (42.3%) and 10 (7.7%) patients were in Class IV and II, respectively. Nearly 34.6% patients had AF, and remaining 63.1% had sinus rhythm. Out of 130 patients, 26 (20%) patients had single-leaflet valve and 103 (79.2%) patients had bileaflet valve, and only one patient had ball and cage type of the valve. Out of 130 patients, 81 (62.3%) patients received fibrinolytic therapy as the first-line therapy and 49 (37.7%) patients underwent surgery initially. In fibrinolytic therapy group, three patients underwent surgery due to failed fibrinolytic therapy. Fifty-three patients (65.5%) had complete hemodynamic and clinical success without any complications; 28 patients (34.5%) had failure. Of 130 patients, 49 patients underwent surgery as the initial treatment. In the surgical group, three patients died out of 52 patients; mortality rate was 5.80%.
Conclusion: Surgery should be offered to patients with contraindications for fibrinolytic therapy as in case of recurrent PHVT surgery offers better outcome with lesser recurrences when compared with fibrinolytic therapy.

Keywords: Prosthetic heart valve thrombosis, surgery, thrombolytic therapy, treatment


How to cite this article:
Mansuri Z, Sharma V, Jain S, Prajapati J, Bhatia S, Patel K. Clinical profile of prosthetic heart valve thrombosis and outcome analysis of fibrinolytic therapy versus surgical management: A single-center experience. Heart India 2020;8:74-9

How to cite this URL:
Mansuri Z, Sharma V, Jain S, Prajapati J, Bhatia S, Patel K. Clinical profile of prosthetic heart valve thrombosis and outcome analysis of fibrinolytic therapy versus surgical management: A single-center experience. Heart India [serial online] 2020 [cited 2020 Sep 19];8:74-9. Available from: http://www.heartindia.net/text.asp?2020/8/2/74/291360




  Introduction Top


Prosthetic valve thrombosis is defined as any obstruction of prosthesis by noninfective thrombotic material or valve–related clotting impairing the function of the valve.[1] Prosthetic valve obstruction or stuck prosthesis covers different pathologies such as the thrombus, pannus, and vegetation.[2] Prosthetic thrombosis is always a serious complication associated with high mortality rate, particularly in obstructive cases thus needs urgent diagnosis and treatment.[3]

The incidence of prosthetic valve thrombosis (PVT) depends on valve type, location of valve, and adequacy of anticoagulation. The incidence of the PVT for mitral valve is five times and for embolism is 1.5 times higher as compared with that of the aortic valve.[2] Inadequate anticoagulation in patients with mechanical heart valve can result in a significant incidence of thromboembolism and prosthetic heart valve thrombosis (PHVT) which average 0.2% and 1.8% patient–year, respectively.[2] Optimal management of these patients with prosthetic valve obstruction is controversial with some advocating fibrinolysis and others surgery. The purpose of the study is to study the efficacy, outcomes, and complications of fibrinolytic therapy and surgery for obstructive PHVT.


  Materials and Methods Top


This was a prospective, observational study conducted in the department of cardiology, from January 2016 to December 2017; a total of 130 patients with PHVT were enrolled. The present study was approved by the Institutional Ethics Committee. We prospectively enrolled the data of patients admitted with valve replacement and having history suggestive of prosthetic valve dysfunction in form of recent onset acute or sub-acute dyspnea (<1 month) or embolic phenomena were subjected to evaluate for PHVT. Patients with confirmed diagnosis of valve thrombosis either by transthoracic/transesophageal echocardiography or cinefluoroscopy were included in our study. Patients with gradual or chronic history suggestive of valve dysfunction were excluded. Patients with prosthetic valve endocarditis were also excluded. Written informed consent was taken from all the participants.

Routine blood investigations included complete hemogram, liver, and renal function tests. Prothrombin time with international normalized ratio (INR) was done on admission and previous record of anticoagulation was noted if available. On admission, detailed transthoracic echo evaluation was performed. For mitral prostheses, a mean gradient >10 mm Hg and an effective area (<1.3 cm2) is indicative of PHVT. For aortic prostheses, criterion for PHVT is a mean gradient >45 mm Hg. Serial echocardiography was performed after fibrinolytic therapy to evaluate the resolution of thrombus and transprosthetic gradient.

In fibrinolytic therapy group, all details of thrombolytic therapy were noted. (e.g., thrombolytic agent, dose, duration, and complications, etc.). Streptokinase (SK) and urokinase (UK) have been the most commonly used thrombolytic agents. Patients with known allergy to SK or those who have been exposed previously to SK were given UK.

Fibrinolytic regimen

SK: 250,000-U bolus given in 30 min, followed by an infusion of 100,000 U/h.

UK: 4400 U/kg bolus over 30 min followed by 4400 U/kg/h.

Statistical analysis

All statistical studies were carried out using IBM SPSS version 20.0 (Chicago, IL, USA). Quantitative variables were expressed as the mean ± standard deviation, and qualitative variables were expressed as percentage (%). Parametric values between the two groups were performed using the independent sample t-test or Chi-square test, as appropriate. Categorical variables were compared using the Chi-square test. A nominal significance was taken as a two-tailed P < 0.05. For the assessment of outcome, the endpoints were recurrence and death. The cumulative survival plot in relation to the treatment (fibrinolytic or surgery) was estimated using the Kaplan–Meier method with use of the log-rank test. Hazard ratio is measured by cox-regression analysis.


  Results Top


The population consisted of 43 (33.1%) males and 87 (66.9%) females, with a mean age of 38.37 ± 12.47. The range of average hospital stay of 130 patients was 0–28 days with 9.5 mean days. Average duration from the surgery for valve replacement was 756 days (25.20 months). Patients divided in various groups, 3 months-6 months-12 months and more than 12 months. Seventy-two (55.4%) patients presented after 12 months of surgery and 58 (44.6%) patients presented within 1 year of the first surgery. Detail of preoperative surgery and valve is showed in [Table 1]. Eighty-percent patients had bi-leaflet metallic valve, whereas 20% patients had single-leaflet valve. In the surgery group, success rate was higher (84.6% vs. 79%) in patients with bi-leaflet valve.
Table 1: Preoperative indication of valvular surgery and valve details (n=130)

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Among 130 patients, most of the patients were New York Heart Association (NYHA) Class III (50%) and IV (42.3%), only 7.7% were NYHA Class-II. Mortality was significantly higher in NYHA Class IV (23.6%) patients as compared to Class II or III patients (P = 0.007 and 0.04). Success rate of thrombolysis is dependent on functional class. Higher the functional class, higher mortality and lower the success rate is showed in [Table 2]. Thus, NYHA functional class is an independent strong predictor of outcome of patient irrespective of treatment modality.
Table 2: Correlation of thrombolysis efficacy according to the functional class

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Every patient was tested on admission for prothrombin time and INR. Out of 130 patients 88 patients (67.70%) were inadequate anticoagulated on admission while 42 (32.30%) patients admitted with adequate anticoagulation. Patients were investigated for anticoagulation status and routine blood test for anemia, liver, and renal function. Out of 130 patients, 59 patients (45.4%) had anemia. Forty patients (30.7%) and 22 patients (15.4%) had altered liver and renal function, respectively. Liver function was altered due to congestive heart failure and itself is risk factor for anticoagulant toxicity. Renal function deranged due to forward cardiac failure.

Echocardiography

Each patient underwent detailed echocardiography evaluation and was evaluated serially for treatment monitoring. Majority of patients (69.2%) had dilated left atrium on admission. Nearly 73.8% of patients had good left ventricular (LV) function, only 12.4% patients had moderate-to-severe LV dysfunction. Around 44.6% patients had moderate-to-severe Pulmonary arterial hypertension (PAH) on admission. After treatment, only 8.7% patients had residual moderate PAH. Transesophageal echocardiography (TEE) is more helpful to rule out pannus formation or nonthrombotic causes for prosthetic valve dysfunction. Additional CF and TEE were used in 93 (71.5%) and 9 (6.9%) patients, respectively. In 23 (17.8%) patients, both CF and TEE were used.

Among 130 patients, 81 (62.3%) patients were enrolled in fibrinolytic therapy group, and 49 (37.7%) were in the surgery group. In fibrinolytic therapy group, three patients underwent surgery due to failed fibrinolytic therapy. SK was used in 72 patients out of 79 patients, whereas UK was used in nine patients. The duration of fibrinolytic therapy was ranged from 1 to 48 h. The average duration of fibrinolytic therapy was 33.09 h. Criteria to stop fibrinolytic therapy were clinical and hemodynamic improvement. One patient had an allergy with SK initially, and hence UK was given. After fibrinolytic therapy, patients were divided into three groups according to clinical, hemodynamic improvement, and complications of fibrinolytic therapy.

In fibrinolytic therapy group, 53 patients (65.5%) had complete hemodynamic and clinical success without any complications and 28 patients (34.5%) had failure. Out of these 28 patients, 16 patients had success with complication due to fibrinolytic therapy, nine patients had partial success, and in three patients had no improvement. Three patients from partial success group underwent surgery later on. Twelve patients died in the fibrinolytic therapy group. Overall mortality was 11.27% in our study. In fibrinolytic therapy group, out of 81 patients, 12 patients died. Mortality rate of fibrinolytic therapy group was 14.80% showed in [Table 3]. The survival plot in relation to treatment (fibrinolytic or surgery) was estimated showed in [Figure 1].
Table 3: Comparison of both groups

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Figure 1: Kaplan–Meier analysis of overall survival among patients treated by surgery (blue line) and fibrinolysis (green line). Total death,P= 0.03, hazards ratio 1.33 and 95% confidence interval 95% (0.93–1.92)

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In surgical group, 48 patients (92.3%) had complete success, one patient had complications, and three patients died; out of 52 patients, mortality rate were 5.70%. The detail of surgery performed is mentioned in [Table 4].
Table 4: Details of surgery performed (n=52)

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A total of 115 patients were followed up to 6 months after the discharge. Out of 115, 19 patients developed the recurrence of PHVT, of which six patients expired. Recurrence rate was higher among the fibrinolytic therapy group as compared with the surgery group. A major disadvantage of thrombolytic therapy is the relatively high incidence of recurrent thrombosis during follow-up is showed in [Table 5]. Out of 17 recurrences, episode in fibrinolytic therapy group and surgery group 12 versus 1 episode were treated with fibrinolytic therapy. Out of them, 5 versus one patient expired; mortality was 6.2% versus 1.9 which was lower than combined overall mortality. Fibrinolytic therapy for a recurrent episode of PHVT is not as efficacious as it is for the first episode and causes more adverse events.
Table 5: Six months follow-up of patients with prosthetic heart valve thrombosis

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In univariate analysis, factors associated with mortality were fibrinolysis, surgery, complication, and NYHA functional class (P = 0.004). No association was observed for age, sex, palpitation, and valve type. In multivariate analysis, by logistic regression, the only factor associated with mortality was NYHA functional class (P = 0.001).


  Discussion Top


Majority of the patient in our study was relatively young. Around 60% patients were below 40 years of age. The reason for this is a high prevalence of rheumatic heart disease in young patients in our country and that's why majority of patients undergoing valve replacement are relatively young compared to developed countries.

PHVT is a serious complication of valvular replacement and its optimal management remains controversial. This tertiary care single-center study is comparing thrombolytic therapy and surgical treatment in patients with Prosthetic heart valve obstruction (PHVO). According to the 2007 European Society of Cardiology and the 2008 American College of Cardiology/American Heart Association guidelines, surgery is the treatment of choice of left-sided OPVT.[4] The management of PVT is predominantly surgical intervention especially for left-sided valves. Thrombolytic therapy is an alternative to surgical treatment.[5] It is associated with lower mortality rate but carries the risk of systemic embolism, bleeding, and rethrombosis. Roudaut et al. in the largest single-center nonrandomized retrospective study cited better early success rate and a significant lower incidence of complications for postsurgical than postfibrinolytic therapy in left-sided OPVT.[6]

In our study, most cases had mitral valve thrombosis (91.5%), whereas 8.5% patients had aortic prosthesis thrombosis. In a study by Gupta et al., 87.3% of the PVT episodes occurred in the mitral position. Several studies have confirmed that mitral PVT is 2–3 times more frequent than thrombosis of an aortic prosthesis.[5] A search of at least 200 published reports of left-sided prosthetic valve fibrinolytic therapy showed an 82% initial success rate, an overall thromboembolism rate of 12%, and a stroke rate of 5%–10%, with 6% death, 5% major bleeding episodes, and 11% recurrent thrombosis.[7],[8],[9],[10]

Complete success defined as complete hemodynamic and clinical recovery was achieved in 53 patients (65.5%) without any major complications. While in 16 patients success achieved at the cost of major thromboembolic complication. Three patients later on underwent surgery. We could not take follow-up of rest of the three patients. In three patients (3.7%), fibrinolytic therapy was ineffective, and these three patients died. Overall success rate of fibrinolytic therapy was 65.5%, and mortality was 14.8% in our study. Roudaut et al. reported in their study that full success with one or more consecutive thrombolytic regimens was obtained in 90 out of 127 cases (70.9%): 37/46 (80%) aortic valve and 52/80 (65%) mitral valve.[6] In our study, majority of cases (88.5%) were with mitral valve.

Hering et al. reported in their study that fibrinolytic therapy resulted in complete clinical and hemodynamic recovery in approximately 76% of patients with left-sided and 71% of those with tricuspid PVT.[11] Success rates were slightly higher in aortic than in mitral valve prostheses, probably because of the greater degree of thrombotic burden necessary to cause significant obstruction in mitral valve prostheses.[12]

Atrial fibrillation is one of the major causes for thromboembolism, and it is also risk factor for PVT. In our study, around 36.9% patients had atrial fibrillation or flutter, and remaining 63.1% had sinus rhythm. Here, we have relatively higher prevalence of atrial fibrillation and flutter in PHVT patients.

Variation in perioperative mortality between reported series reflects the differences in clinical condition at the time of surgery, priority of operation (elective vs. emergent), and year of operation. Out of 52 surgeries, 39 (75%) surgeries were performed emergency base and 13 (25%) were performed elective base. Roudaut et al.'s study shows surgery succeeded in 89% of the patients.[6] The early mortality rate was 10.3%. The overall incidence of complications (hemorrhage, embolism, and death) was 11.1% (P, 0:01). In our study, surgery succeeded in 92.3% of the patients (P ≤ 0.001). The mortality rate was 5.7%, and incidence of complication (atrial fibrillation) was 1.9% (P = 0.04).

A major disadvantage of thrombolytic therapy is the relatively high incidence of recurrent thrombosis during the follow-up. In our study, recurrence rate was around 20.99% in fibrinolytic therapy group and 3.85% in the surgery group. According to one meta-analysis, recurrent thrombosis was observed in 20% after fibrinolytic therapy as compared with 3% after valve re-replacement.[11],[13]

High recurrence is related to patient's compliance to the medicines, genotypic difference in warfarin metabolism. Out of 17 recurrences episode in fibrinolytic therapy group and surgery group, 12 versus 1 episodes were treated with fibrinolytic therapy. Out of them, 5 versus 1 patient expired; mortality was 6.2% versus 1.9 which was lower than combined overall mortality. Fibrinolytic therapy for a recurrent episode of PHVT is not as efficacious as it is for the first episode and causes more adverse events. These patients have a greater tendency for repeated PHVT after fibrinolytic therapy than when managed by thrombectomy (8%) or valve replacement (3%).[14] It is possible that thrombolytic therapy does not completely remove all of the thrombus from the valve, resulting in persistent abnormal flow patterns acting as a substrate for subsequent thrombosis. Ideally, recurrent episodes are best treated with the surgery.[14]


  Conclusion Top


NYHA functional class, LV function, site of valve, and recurrent episodes are the major determinants of success of fibrinolytic therapy. Until randomized clinical trials are performed, there is no evidence that either of the two treatment options offers any substantial advantage over the other. However, in our study, we found that surgery offers better success rate and lesser recurrences. Surgery whenever feasible should be offered to patients with contraindications for fibrinolytic therapy as well as recurrent PHVT as surgery offers better outcome as well as lesser recurrences when compared with fibrinolytic therapy. Although extended follow-up of these patients will provide critical data so as to decide which modality offers better outcome.

Acknowledgment

All the authors acknowledge the help and support received from the U. N. Mehta Institute of Cardiology and Research Centre and its staff for providing all the data and resources. We are truly indebted to our patients who provide us with the invaluable support and permission even through their suffering and ill health.

Financial support and sponsorship

This work was financially supported by U. N. Mehta Institute of Cardiology and Research Center itself and received no specific grant from any funding agency, commercial, or not for profit sectors.

Conflicts of interest

There are no conflicts of interest.

Ethical Approval

The study involves human participants;the studies has been approved by the appropriate institutional ethics committee (UNMICRC/CARDIO/2015/82) and has been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. This article does not contain study performed on animals by any of the authors.



 
  References Top

1.
Shapira Y, Herz I, Vaturi M, Porter A, Adler Y, Birnbaum Y, et al. Fibrinolytic therapy is an effective and safe therapy in stuck bileaflet mitral valves in the absence of high-risk thrombi. J Am Coll Cardiol 2000;35:1874-80.  Back to cited text no. 1
    
2.
Inamdar A, Shende SP, Inamdar S. Prosthetic valve obstruction: Redo surgery or fibrinolysis? Med J DY Patil Univer 2017;10:246.  Back to cited text no. 2
    
3.
Bonou M, Lampropoulos K, Barbetseas J. Prosthetic heart valve obstruction: Thrombolysis or surgical treatment? Eur Heart J Acute Cardiovasc Care 2012;1:122-7.  Back to cited text no. 3
    
4.
Vigoda MM, Sweitzer B, Miljkovic N, Arheart KL, Messinger S, Candiotti K, et al. 2007 American College of Cardiology/American Heart Association (ACC/AHA) Guidelines on perioperative cardiac evaluation are usually incorrectly applied by anesthesiology residents evaluating simulated patients. Anesth Analg 2011;112:940-9.  Back to cited text no. 4
    
5.
Hirachan A, Roka M, Prajapati D, Adhikari CM, Bishal KC, Khadka MB, et al. Prosthetic valve thrombosis in a tertiary cardiac centre. Nepalese Heart J 2017;14:9-11.  Back to cited text no. 5
    
6.
Roudaut R, Lafitte S, Roudaut MF, Reant P, Pillois X, Durrieu-Jaïs C, et al. Management of prosthetic heart valve obstruction: Fibrinolysis versus surgery. Early results and long-term follow-up in a single-centre study of 263 cases. Arch Cardiovasc Dis 2009;102:269-77.  Back to cited text no. 6
    
7.
Sato N, Miura M, Itoh T, Ohmi M, Haneda K, Mohri H, et al. Sound spectral analysis of prosthetic valvular clicks for diagnosis of thrombosed Björk-Shiley tilting standard disc valve prostheses. J Thorac Cardiovasc Surg 1993;105:313-20.  Back to cited text no. 7
    
8.
Ledain LD, Ohayon JP, Colle JP, Lorient-Roudaut FM, Roudaut RP, Besse PM. Acute thrombotic obstruction with disc valve prostheses: Diagnostic considerations and fibrinolytic treatment. J Am Coll Cardiol 1986;7:743-51.  Back to cited text no. 8
    
9.
Czer LS, Weiss M, Bateman TM, Pfaff JM, DeRobertis M, Eigler N, et al. Fibrinolytic therapy of St. Jude valve thrombosis under guidance of digital cinefluoroscopy. J Am Coll Cardiol 1985;5:1244-9.  Back to cited text no. 9
    
10.
Lengyel M, Fuster V, Keltai M, Roudaut R. Guidelines for management of left-sided prosthetic valve thrombosis: A role for thrombolytic therapy. J Am Coll Cardiol 1997;6:1521-6.  Back to cited text no. 10
    
11.
Hering D, Piper C, Horstkotte D. Management of prosthetic valve thrombosis. Eur Heart J Supp 2001;3 Suppl Q:Q22-6.  Back to cited text no. 11
    
12.
Birdi I, Angelini GD, Bryan AJ. Thrombolytic therapy for left sided prosthetic heart valve thrombosis. J Heart Valve Dis 1995;4:154-9.  Back to cited text no. 12
    
13.
Gupta D, Kothari SS, Bahl VK, Goswami KC, Talwar KK, Manchanda SC, et al. Thrombolytic therapy for prosthetic valve thrombosis: Short- and long-term results. Am Heart J 2000;140:906-16.  Back to cited text no. 13
    
14.
Balasundaram RP, Karthikeyan G, Kothari SS, Talwar KK, Venugopal P. Fibrinolytic treatment for recurrent left sided prosthetic valve thrombosis. Heart 2005;91:821-2.  Back to cited text no. 14
    


    Figures

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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